Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

Systematic selection of competing metabolomics methods in a metabolite-sensory relationship study

Introduction The relationship between the chemical composition of food products and their sensory profile is a complex association confronting many challenges. However, new untargeted methodologies are helping correlate metabolites with sensory characteristics in a simpler manner. Nevertheless, in the pilot phase of a project, where only a small set of products areused to explore the relationships, choices have to be made about the most appropriate untargeted metabolomics methodology.Objective To provide a framework for selecting a metabolite-sensory methodology based on: the quality of measurements, the relevance of the detected metabolites in terms of distinguishing between products or in terms of whether they can be related to the sensory attributes of the products.Methods In this paper we introduce a systematic approach to explore all these different aspects driving the choice for the most appropriate metabolomics method.Results As an example we have used a tomato soup project where the choice between two sampling methods (SPME and SBSE) had to be made. The results are not always consistently pointing to the same method as being the best. SPME was able to detect metabolites with a better precision, SBSE seemed to be able to provide a better distinction between the soups.Conclusion The three levels of comparison provide information on how the methods could perform in a follow up study and will help the researcher to make a final selection for the most appropriate method based on their strengths and weaknesses